There are six subgroups of the human adenoviruses (A-F). It has been reported that human adenovirus type 9 (a group D virus) induces benign breast firbroadenomas in inbred Wistar/Furth rats. Tumor latencies are three to five months and incidences 100%. Only female rats are affected. Ad9 is as tumorigenic in adult females as in newborns. We propose to repeat these results, to extend them to other members of the group D of the human adenoviruses, and to determine the state, nature of expression, and location of the viral sequences in tumor tissue. Involvement of Ad9-induced retroviral sequences or Ad9-induced cellular tumor-growth promoting factors will be examined. The hormone-dependency of the tumors will be examined through the use of ovariectomized animals and estrogen and prolactin levels in tumor bearing animals will be measured by RIA and compared to normal values. Very little is known about group D of the human adenoviruses. Extensive characterization of the Ad9 genome will be undertaken including restriction and transcription maps, comparative studies to the other groups by EM heteroduplex analysis, and DNA sequence analysis of important segments of the viral DNA. Ad9 will also be compared to the other members of group D by heteroduplex analysis. Viral host-range mutants will be isolated in regions of the viral genome which might be involved in tumor induction and screened for oncogenicity. Along with mouse mammary tumor virus (MMTV), human adenovirus type 9 is the only virus to induce with high efficiency and specificity a tumor of clinical relevance to the human population. Our goal is a molecular understanding of this unique oncogenic potential.